Program Project Grant research has identified several signaling proteins that modulate behavioral responses to drugs of abuse or are themselves modulated by chronic drug exposure. The purpose of the Behavioral Core is to provide a high-throughput, behavior screen to characterize the role played by these proteins in several relatively straightforward drug- related behaviors that are thought to model aspects of drug addiction. In these studies, a protein of interest will be modulated by 1) by intracerebral injection of activators or inhibitors; 2) by direct transfection of neurons with viral vectors over expressing the protein of interest; or 3) by using genetic mutant mice that lack or over express the protein of interest (see Transgenic Core). The effects of modulating the target protein will then be tested in one or more of the following behavioral models: 1) novelty-seeking behavior in drug-naive animals, a trait thought to predict and perhaps contribute to individual differences in drug abuse; 2) locomotor sensitization to cocaine or morphine, a behavioral phenomenon thought to result from neuroplasticity in the mesolimbic dopamine system following repeated exposure to drugs of abuse; 3) opiate physical withdrawal, where specific behaviors are thought to reflect the neuroadaptations of opiate dependence in discrete brain regions, including the locus coeruleus; and 4) place conditioning to cocaine or morphine, which provides an indirect measure of the rewarding effects of initial periods of drug exposure, as well as conditioned place aversion in opiate-dependent animals, which measures the aversive consequence of opiate withdrawal; both behaviors are thought to involve altered neurotransmission in the nucleus accumbens and related limbic structures. The Behavioral Core will thereby provide investigators in the individual Projects of this grant with a repertoire of behavioral assays. The goal is to enable investigators to relate the molecular and cellular phenomena that form the foundation of our program of research to specific and functionally relevant behavioral endpoints related to drug addiction. Ultimately, a smaller number of molecular events will be studied in the more complex behavioral models of drug self-administration, relapse, and conditioned reinforcement that form the basis of Project 4. By consolidating more routine behavioral assays in this Core, we ensure quality control of the assays and the ability to relate behavioral findings in one Project to another, as well as facilitate the integration of molecular, cellular, and behavioral levels of analysis, a major objective of our Program Project Grant.